Hedgehog signaling is required for primary motoneuron induction in zebrafish

Sonic hedgehog (Shh) is crucial for motoneuron development in chick and mou se. However, zebrafish embryos homozygous for a deletion of the shh locus h ave normal numbers of motoneurons, raising the possibility that zebrafish m otoneurons may be specified differently. Unlike other vertebrates, zebrafis h express three hh genes in the embryonic midline: shh, echidna hedgehog (e hh) and tiggywinkle hedgehog (twhh). Therefore, it is possible that Twhh an d Ebb are sufficient for motoneuron formation in the absence of Shh. To tes t this hypothesis we have eliminated, or severely reduced, all three Hh sig nals using mutations that directly or indirectly reduce Hh signaling and an tisense morpholinos. Our analysis shows that Hh signals are required for ze brafish motoneuron induction. However, each of the three zebrafish Hhs is i ndividually dispensable for motoneuron development because the other two ca n compensate for its loss. Our results also suggest that Twhh and Shh are m ore important for motoneuron development than Ehh.